{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:50:13Z","timestamp":1792029013512,"version":"4.4.0"},"reference-count":103,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T00:00:00Z","timestamp":1660521600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although sepsis and acute kidney injury (AKI) have a bidirectional interplay, the pathophysiological mechanisms between AKI and sepsis are not clarified and worthy of a comprehensive and updated review. The primary pathophysiology of sepsis-associated AKI (SA-AKI) includes inflammatory cascade, macrovascular and microvascular dysfunction, cell cycle arrest, and apoptosis. The pathophysiology of sepsis following AKI contains fluid overload, hyperinflammatory state, immunosuppression, and infection associated with kidney replacement therapy and catheter cannulation. The preventive strategies for SA-AKI are non-specific, mainly focusing on infection control and preventing further kidney insults. On the other hand, the preventive strategies for sepsis following AKI might focus on decreasing some metabolites, cytokines, or molecules harmful to our immunity, supplementing vitamin D3 for its immunomodulation effect, and avoiding fluid overload and unnecessary catheter cannulation. To date, several limitations persistently prohibit the understanding of the bidirectional pathophysiologies. Conducting studies, such as the Kidney Precision Medicine Project, to investigate human kidney tissue and establishing parameters or scores better to determine the occurrence timing of sepsis and AKI and the definition of SA-AKI might be the prospects to unveil the mystery and improve the prognoses of AKI patients.<\/jats:p>","DOI":"10.3390\/ijms23169159","type":"journal-article","created":{"date-parts":[[2022,8,15]],"date-time":"2022-08-15T20:58:08Z","timestamp":1660597088000},"page":"9159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":112,"title":["Sepsis and Acute Kidney Injury: A Review Focusing on the Bidirectional Interplay"],"prefix":"10.3390","volume":"23","author":[{"given":"Yu-Ming","family":"Chang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Camillian Saint Mary\u2019s Hospital Luodong, Yilan 26546, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chih","family":"Kan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan"},{"name":"Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan 71703, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-7574","authenticated-orcid":false,"given":"Chih-Chung","family":"Shiao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Camillian Saint Mary\u2019s Hospital Luodong, Yilan 26546, Taiwan"},{"name":"Saint Mary\u2019s Junior College of Medicine, Nursing and Management, Yilan 26546, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2215\/CJN.06480612","article-title":"Association between AKI, recovery of renal function, and long-term outcomes after hospital discharge","volume":"8","author":"Pannu","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/ki.2011.259","article-title":"Acute-on-chronic kidney injury at hospital discharge is associated with long-term dialysis and mortality","volume":"80","author":"Wu","year":"2011","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1681\/ASN.2017070765","article-title":"Clinical Decision Support for In-Hospital AKI","volume":"29","author":"Dealmeida","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO clinical practice guidelines for acute kidney injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin Pr."},{"key":"ref_6","first-page":"749","article-title":"Nomenclature and diagnostic criteria for acute kidney injury\u20142020 consensus of the Taiwan AKI-task force","volume":"121","author":"Yang","year":"2022","journal-title":"J. Med. Assoc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1038\/ki.2011.241","article-title":"The distant organ effects of acute kidney injury","volume":"81","author":"Grams","year":"2012","journal-title":"Kidney Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/MCC.0000000000000150","article-title":"Systemic consequences of acute kidney injury","volume":"20","author":"Druml","year":"2014","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2215\/CJN.01300216","article-title":"Biomarkers for the Early Detection and Prognosis of Acute Kidney Injury","volume":"12","author":"Malhotra","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1093\/ndt\/gft510","article-title":"A basic science view of acute kidney injury biomarkers","volume":"29","author":"Charlton","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1016\/j.kint.2019.05.026","article-title":"Acute kidney injury from sepsis: Current concepts, epidemiology, pathophysiology, prevention and treatment","volume":"96","author":"Peerapornratana","year":"2019","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"R231","DOI":"10.1186\/cc13054","article-title":"Risk of developing severe sepsis after acute kidney injury: A population-based cohort study","volume":"17","author":"Lai","year":"2013","journal-title":"Crit. Care"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.ccc.2020.11.010","article-title":"Sepsis-Associated Acute Kidney Injury","volume":"37","author":"Gomez","year":"2021","journal-title":"Crit. Care Clin."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liu, D., Su, L., Han, G., Yan, P., and Xie, L. (2015). Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0129450"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Huang, Y.T., Lai, M.Y., Kan, W.C., and Shiao, C.C. (2020). Independent Predictive Ability of Procalcitonin of Acute Kidney Injury among Critically Ill Patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061939"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/01.CCM.0000194725.48928.3A","article-title":"Sepsis in European intensive care units: Results of the SOAP study","volume":"34","author":"Vincent","year":"2006","journal-title":"Crit. Care Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.2215\/CJN.02140215","article-title":"Epidemiology and Clinical Correlates of AKI in Chinese Hospitalized Adults","volume":"10","author":"Xu","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1164\/rccm.201505-0995OC","article-title":"The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock","volume":"193","author":"Kellum","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Selby, N.M., Kolhe, N.V., McIntyre, C.W., Monaghan, J., Lawson, N., Elliott, D., Packington, R., and Fluck, R.J. (2012). Defining the cause of death in hospitalised patients with acute kidney injury. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0048580"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1046\/j.1523-1755.2003.00040.x","article-title":"Renal dysfunction and serious infections after open-heart surgery","volume":"64","author":"Thakar","year":"2003","journal-title":"Kidney Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1016\/j.jtcvs.2019.11.004","article-title":"Stage 1 acute kidney injury is independently associated with infection following cardiac surgery","volume":"161","author":"Griffin","year":"2021","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Griffin, B.R., You, Z., Holmen, J., SooHoo, M., Gist, K.M., Colbert, J.F., Chonchol, M., Faubel, S., and Jovanovich, A. (2019). Incident infection following acute kidney injury with recovery to baseline creatinine: A propensity score matched analysis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217935"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wu, V.C., Wang, C.Y., Shiao, C.C., Chang, C.H., Huang, H.Y., Huang, T.M., Lai, C.F., Lin, M.C., Ko, W.J., and Wu, K.D. (2013). Increased risk of active tuberculosis following acute kidney injury: A nationwide, population-based study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069556"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1097\/CCM.0b013e3181a03961","article-title":"Epidemiology of infection in critically ill patients with acute renal failure","volume":"37","author":"Reynvoet","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1164\/rccm.201511-2285OC","article-title":"Structure and Function of the Kidney in Septic Shock. A Prospective Controlled Experimental Study","volume":"194","author":"Maiden","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1097\/CCM.0000000000003507","article-title":"Effects of Fluid Bolus Therapy on Renal Perfusion, Oxygenation, and Function in Early Experimental Septic Kidney Injury","volume":"47","author":"Lankadeva","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e897","DOI":"10.1097\/CCM.0000000000001735","article-title":"Histopathology of Septic Acute Kidney Injury: A Systematic Review of Experimental Data","volume":"44","author":"Kosaka","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1681\/ASN.2011020203","article-title":"Endotoxin uptake by S1 proximal tubular segment causes oxidative stress in the downstream S2 segment","volume":"22","author":"Kalakeche","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s13054-016-1219-3","article-title":"Detrimental cross-talk between sepsis and acute kidney injury: New pathogenic mechanisms, early biomarkers and targeted therapies","volume":"20","author":"Dellepiane","year":"2016","journal-title":"Crit. Care"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R1226","DOI":"10.1152\/ajpregu.00228.2015","article-title":"Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep","volume":"309","author":"Calzavacca","year":"2015","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(19)32563-2","article-title":"Acute kidney injury","volume":"394","author":"Ronco","year":"2019","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.kint.2016.07.032","article-title":"Renal perfusion in sepsis: From macro- to microcirculation","volume":"91","author":"Post","year":"2017","journal-title":"Kidney Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13054-015-0741-z","article-title":"Glycocalyx and sepsis-induced alterations in vascular permeability","volume":"19","author":"Chelazzi","year":"2015","journal-title":"Crit. Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.bpa.2017.10.002","article-title":"The macro- and microcirculation of the kidney","volume":"31","author":"Guerci","year":"2017","journal-title":"Best Pr. Res. Clin. Anaesthesiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.1038\/ncomms5436","article-title":"PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis","volume":"5","author":"Yang","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jss.2014.10.009","article-title":"Adenosine monophosphate-activated protein kinase activation protects against sepsis-induced organ injury and inflammation","volume":"194","author":"Escobar","year":"2015","journal-title":"J. Surg. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1097\/SHK.0000000000000528","article-title":"Pharmacological Sirt1 Activation Improves Mortality and Markedly Alters Transcriptional Profiles That Accompany Experimental Sepsis","volume":"45","author":"Opal","year":"2016","journal-title":"Shock"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1097\/01.sla.0000094387.50865.23","article-title":"Effects of intravenous fluid restriction on postoperative complications: Comparison of two perioperative fluid regimens: A randomized assessor-blinded multicenter trial","volume":"238","author":"Brandstrup","year":"2003","journal-title":"Ann. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"He, J., and Yang, B. (2019). Aquaporins in Renal Diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020366"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/S0034-5687(00)00193-6","article-title":"Aquaporin channels may modulate ventilator-induced lung injury","volume":"124","author":"Hales","year":"2001","journal-title":"Respir. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1093\/ndt\/gfs256","article-title":"Cytokine production increases and cytokine clearance decreases in mice with bilateral nephrectomy","volume":"27","author":"Dursun","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nrneph.2015.158","article-title":"Mechanisms and mediators of lung injury after acute kidney injury","volume":"12","author":"Faubel","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1681\/ASN.2006050494","article-title":"Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury","volume":"18","author":"Hoke","year":"2007","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"C486","DOI":"10.1152\/ajpcell.00419.2006","article-title":"Migration of leukocytes across an endothelium-epithelium bilayer as a model of renal interstitial inflammation","volume":"293","author":"Bijuklic","year":"2007","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1111\/j.1523-1755.2004.66023.x","article-title":"Impaired monocyte cytokine production in critically ill patients with acute renal failure","volume":"66","author":"Himmelfarb","year":"2004","journal-title":"Kidney Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"926","DOI":"10.2215\/CJN.04560514","article-title":"Associations between Intensity of RRT, Inflammatory Mediators, and Outcomes","volume":"10","author":"Murugan","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"595","DOI":"10.3389\/fimmu.2018.00595","article-title":"Innate Immunity in the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome and Its Implications for Therapy","volume":"9","author":"Horiguchi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/ki.2009.502","article-title":"Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival","volume":"77","author":"Murugan","year":"2010","journal-title":"Kidney Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"F864","DOI":"10.1152\/ajprenal.00025.2012","article-title":"Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice","volume":"303","author":"Ahuja","year":"2012","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/ki.2008.648","article-title":"Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury","volume":"75","author":"Awad","year":"2009","journal-title":"Kidney Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.4049\/jimmunol.1103254","article-title":"Lung T lymphocyte trafficking and activation during ischemic acute kidney injury","volume":"189","author":"Lie","year":"2012","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"F421","DOI":"10.1152\/ajprenal.00559.2010","article-title":"Macrophages mediate lung inflammation in a mouse model of ischemic acute kidney injury","volume":"302","author":"Altmann","year":"2012","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1097\/SHK.0b013e31826359d0","article-title":"Lung endothelial cell apoptosis during ischemic acute kidney injury","volume":"38","author":"White","year":"2012","journal-title":"Shock"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.bbrc.2009.08.062","article-title":"Toll-like receptors and innate immunity","volume":"388","author":"Kumar","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1126\/science.285.5425.248","article-title":"HMG-1 as a late mediator of endotoxin lethality in mice","volume":"285","author":"Wang","year":"1999","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1074\/jbc.M306793200","article-title":"Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein","volume":"279","author":"Park","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/ki.2011.201","article-title":"Differential effects of kidney-lung cross-talk during acute kidney injury and bacterial pneumonia","volume":"80","author":"Singbartl","year":"2011","journal-title":"Kidney Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e492","DOI":"10.1097\/CCM.0000000000001472","article-title":"Reversal of Acute Kidney Injury-Induced Neutrophil Dysfunction: A Critical Role for Resistin","volume":"44","author":"Singbartl","year":"2016","journal-title":"Crit. Care Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/ki.2011.125","article-title":"Acute loss of renal function attenuates slow leukocyte rolling and transmigration by interfering with intracellular signaling","volume":"80","author":"Rossaint","year":"2011","journal-title":"Kidney Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.immuni.2014.10.008","article-title":"Leukocyte migration into inflamed tissues","volume":"41","author":"Nourshargh","year":"2014","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Macdonald, S.P., Stone, S.F., Neil, C.L., van Eeden, P.E., Fatovich, D.M., Arendts, G., and Brown, S.G. (2014). Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis\/septic shock in the emergency department. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110678"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"R95","DOI":"10.1186\/cc7925","article-title":"Serum resistin levels in critically ill patients are associated with inflammation, organ dysfunction and metabolism and may predict survival of non-septic patients","volume":"13","author":"Koch","year":"2009","journal-title":"Crit. Care"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.4049\/jimmunol.181.6.3761","article-title":"Resistin inhibits essential functions of polymorphonuclear leukocytes","volume":"181","author":"Cohen","year":"2008","journal-title":"J. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13054-018-2040-y","article-title":"Gut-kidney crosstalk in septic acute kidney injury","volume":"22","author":"Zhang","year":"2018","journal-title":"Crit. Care"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Chou, Y.T., Kan, W.C., and Shiao, C.C. (2022). Acute Kidney Injury and Gut Dysbiosis: A Narrative Review Focus on Pathophysiology and Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073658"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1016\/j.kint.2020.04.048","article-title":"Intestinal microbiota control acute kidney injury severity by immune modulation","volume":"98","author":"Yang","year":"2020","journal-title":"Kidney Int."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"886","DOI":"10.34067\/KID.0007722020","article-title":"Kidney-Gut Crosstalk in AKI","volume":"2","author":"Jo","year":"2021","journal-title":"Kidney360"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/labinvest.2010.151","article-title":"Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy","volume":"91","author":"Park","year":"2011","journal-title":"Lab. Invest."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5421","DOI":"10.4049\/jimmunol.1200581","article-title":"Paneth cell-mediated multiorgan dysfunction after acute kidney injury","volume":"189","author":"Park","year":"2012","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1479-5876-7-28","article-title":"Alterations in vitamin D status and anti-microbial peptide levels in patients in the intensive care unit with sepsis","volume":"7","author":"Jeng","year":"2009","journal-title":"J. Transl. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"G208","DOI":"10.1152\/ajpgi.00398.2007","article-title":"Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier","volume":"294","author":"Kong","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1186\/s13054-014-0660-4","article-title":"Vitamin D deficiency as a risk factor for infection, sepsis and mortality in the critically ill: Systematic review and meta-analysis","volume":"18","author":"Groeneveld","year":"2014","journal-title":"Crit. Care"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"83","DOI":"10.5414\/CNP74083","article-title":"Effect of parathyroid hormone and teriparatide on immune function of human adherent and non-adherent leukocytes","volume":"74","author":"Castellanos","year":"2010","journal-title":"Clin. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1159\/000168284","article-title":"Impaired phagocytosis in dialysis patients: Studies on mechanisms","volume":"11","author":"Alexiewicz","year":"1991","journal-title":"Am. J. Nephrol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1097\/01.mnh.0000447021.51722.2f","article-title":"Fibroblast growth factor 23 in acute kidney injury","volume":"23","author":"Christov","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1172\/JCI83470","article-title":"FGF23 signaling impairs neutrophil recruitment and host defense during CKD","volume":"126","author":"Rossaint","year":"2016","journal-title":"J. Clin. Invest."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fendo.2018.00320","article-title":"Role of Fibroblast Growth Factor-23 in Innate Immune Responses","volume":"9","author":"Fitzpatrick","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1681\/ASN.2014101009","article-title":"Low Vitamin D and High Fibroblast Growth Factor 23 Serum Levels Associate with Infectious and Cardiac Deaths in the HEMO Study","volume":"27","author":"Chonchol","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1681\/ASN.2016040401","article-title":"Fibroblast Growth Factor 23 and the Risk of Infection-Related Hospitalization in Older Adults","volume":"28","author":"Nowak","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1111\/nep.12656","article-title":"Erythropoietin concentration in acute kidney injury is associated with insulin-like growth factor-binding protein-1","volume":"21","author":"Yamashita","year":"2016","journal-title":"Nephrology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/ndt\/gfy394","article-title":"Uromodulin (Tamm-Horsfall protein): Guardian of urinary and systemic homeostasis","volume":"35","author":"Micanovic","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1681\/ASN.2017040409","article-title":"Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney","volume":"29","author":"Micanovic","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1523-1755.2004.00452.x","article-title":"Tamm-Horsfall protein knockout mice are more prone to urinary tract infection: Rapid communication","volume":"65","author":"Bates","year":"2004","journal-title":"Kidney Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1016\/j.juro.2009.01.014","article-title":"Tamm-horsfall protein protects against urinary tract infection by proteus mirabilis","volume":"181","author":"Raffi","year":"2009","journal-title":"J. Urol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"F1066","DOI":"10.1152\/ajprenal.00543.2012","article-title":"Tamm-Horsfall protein translocates to the basolateral domain of thick ascending limbs, interstitium, and circulation during recovery from acute kidney injury","volume":"304","author":"McCracken","year":"2013","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"eaaw3639","DOI":"10.1126\/scitranslmed.aaw3639","article-title":"Circulating uromodulin inhibits systemic oxidative stress by inactivating the TRPM2 channel","volume":"11","author":"LaFavers","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1681\/ASN.2016111162","article-title":"Serum Uromodulin and Mortality Risk in Patients Undergoing Coronary Angiography","volume":"28","author":"Delgado","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"278","DOI":"10.5414\/CN109005","article-title":"Association of urinary uromodulin with kidney function decline and mortality: The health ABC study","volume":"87","author":"Garimella","year":"2017","journal-title":"Clin. Nephrol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ijcard.2016.12.183","article-title":"Serum uromodulin is a predictive biomarker for cardiovascular events and overall mortality in coronary patients","volume":"231","author":"Leiherer","year":"2017","journal-title":"Int. J. Cardiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"F907","DOI":"10.1152\/ajprenal.00107.2011","article-title":"Splenectomy exacerbates lung injury after ischemic acute kidney injury in mice","volume":"301","author":"Altmann","year":"2011","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1038\/ki.2008.97","article-title":"AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality","volume":"73","author":"Doi","year":"2008","journal-title":"Kidney Int."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1097\/01.ASN.0000110182.14608.0C","article-title":"Effect of nosocomial bloodstream infection on the outcome of critically ill patients with acute renal failure treated with renal replacement therapy","volume":"15","author":"Hoste","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"224","DOI":"10.5301\/ijao.5000587","article-title":"Infection in critically ill pediatric patients on continuous renal replacement therapy","volume":"40","author":"Santiago","year":"2017","journal-title":"Int. J. Artif. Organs."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1711586","article-title":"Balanced Crystalloids versus Saline in Noncritically Ill Adults","volume":"378","author":"Self","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1056\/NEJMoa1711584","article-title":"Balanced Crystalloids versus Saline in Critically Ill Adults","volume":"378","author":"Semler","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13613-015-0095-3","article-title":"Prevention and treatment of sepsis-induced acute kidney injury: An update","volume":"5","author":"Honore","year":"2015","journal-title":"Ann. Intensive Care"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1007\/s00134-013-2906-z","article-title":"Intra-abdominal hypertension and the abdominal compartment syndrome: Updated consensus definitions and clinical practice guidelines from the World Society of the Abdominal Compartment Syndrome","volume":"39","author":"Kirkpatrick","year":"2013","journal-title":"Intensive Care Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/bph.13417","article-title":"Anti-oxidative effect of AST-120 on kidney injury after myocardial infarction","volume":"173","author":"Fujii","year":"2016","journal-title":"Br. J. Pharm."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Nguyen, H.B., Eshete, B., Lau, K.H., Sai, A., Villarin, M., and Baylink, D. (2013). Serum 1,25-dihydroxyvitamin, D. An outcome prognosticator in human sepsis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064348"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"630951","DOI":"10.3389\/fnut.2020.630951","article-title":"Vitamin D and Acute Kidney Injury: A Two-Way Causality Relation and a Predictive, Prognostic, and Therapeutic Role of Vitamin D","volume":"7","author":"Graidis","year":"2020","journal-title":"Front. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ki.2014.62","article-title":"The high-mobility group protein B1-Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy","volume":"86","author":"Doi","year":"2014","journal-title":"Kidney Int."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40635-017-0150-5","article-title":"Hemoadsorption corrects hyperresistinemia and restores anti-bacterial neutrophil function","volume":"5","author":"Bonavia","year":"2017","journal-title":"Intensive Care Med. Exp."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.kint.2020.08.039","article-title":"Rationale and design of the Kidney Precision Medicine Project","volume":"99","author":"Alpers","year":"2021","journal-title":"Kidney Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9159\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:09:00Z","timestamp":1760141340000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,15]]},"references-count":103,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23169159"],"URL":"https:\/\/doi.org\/10.3390\/ijms23169159","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,15]]}}}